The intravenous injection of F1 hybrid mice on the C57BL/10 background with parental spleen cells resulted in a loss in the ability of the F1 mice to generate T-cell mediated cytotoxic responses in vitro to TNP-self and alloantigens. The total abolition of response potential occurred within 7 days of injection, persisted for at least three weeks, and could be induced with as few as 2 times 10 to the 6th power spleen cells. The loss of response potential depended on the H-2 type of the parental cells, since H-2k,a spleen cells induced unresponsiveness, whereas H-2b spleen cells did not. The phenomenon is: (a) strain-specific (possibly depending on the C57Bl/10 genetic background), since strains of mice with other genetic backgrounds injected with parental cells do not exhibit the loss of immune potential; and (b) dependent on a reaction against F1 alloantigens by grafted parental cells (GVH), since loss of immune activity was associated with enlarged F1 host spleens. Heterogeneous populations of suppressor cells were found to be responsible for loss of immune potential.